Shida Yousefi - Academia.edu (original) (raw)

Papers by Shida Yousefi

Cancer Research

Swainsonine, an inhibitor of a-mannosidases, has been shown to block experimental metastasis of H... more Swainsonine, an inhibitor of a-mannosidases, has been shown to block experimental metastasis of H161 10 melanoma and MDAY-D2 lymphoid tumor cells in syngeneic mice. In this report we demonstrate that swainsonine also reduces the growth rate of human melanoma cells in vitro and in vivo. Graded doses of Swainsonine were administered either orally or via implanted Alzet miniosmotic pumps to athymic nude mice bearing subcutaneously implanted human MeWo melanoma cells. Swainsonine at 10 «ig/ml in the drinking water or 0.5 mg/kg/day administered by miniosmotic pump reduced the growth rate of the Me\Yo tumors by approximately 50% and inhibited the expression of complex-type oligosaccharides in tumors and host intestine by only 10-20%. Swainsonine doses of 4 mg/kg/day reduced expression of complex-type oligosaccharides by 85% in vivo but afforded no additional inhibitory effect. A glycosylation mutant of MeWo called 3S5 has a defect in the synthesis of complex-type asparagine-linked oligosaccharides resulting in incom plete processing similar to that observed in swainsonine-treated MeWo tumor cells. Swainsonine did not inhibit the proliferation of 3S5 cells in vitro nor the growth of 3S5 tumors in nude mice. The results suggest that expression of highly branched complex-type oligosaccharides com monly associated with the malignant phenotype may provide the tumor cells with a growth advantage.

Cancer Research

Sialylated and G\cNAcßl-6Manal-6Manßl (pil-k branched) com plex-type oligosaccharides linked to... more Sialylated and G\cNAcßl-6Manal-6Manßl (pil-k branched) com plex-type oligosaccharides linked to asparagine residues of membrane glycoproteins in metastatic murine tumor cells have been associated with efficient tumor cell metastasis. A large proportion of these oligosaccharide structures, in several unrelated malignant cell lines, have been shown to be associated with a glycoprotein termed P2B, with a molecular weight of 130,000. This glycoprotein has recently been purified from the met astatic MDAY-D2 cell line and shown to be biochemically similar to a lysosomal associated membrane glycoprotein (LAMP-1). We report here the details of a 2147 nucleotide complementary DNA encoding the entire murine P2B polypeptide which was immunoselected from a Xgtl 1 expres sion library and sequenced. The sequence is similar to a complementary DNA coding for mouse LAMP-1 with the exception of a 5' untranslated region, a leader signal-sequence, and various insertions, deletions, and substitutions in the 3' untranslated domain. An open reading frame of 405 amino acids encodes a mature polypeptide of 382 residues with a predicted molecular weight of 42,000. P2B/LAMP-1 possesses 20 asparagine-linked glycosylation sites separated into equal halves by a central, putative hinge region and is anchored by a carboxy, membranespanning, domain. Topologica! considerations dictate that cell surface expression of P2B/LAMP-1 exposes the bulk of the glycoprotein into the extracellular compartment. Immunofluorescent staining of fibroblast cells indicated that P2B/LAMP-1 was associated with lysosomal mem branes and, to a lesser degree, select surfaces of plasma membrane. An amino acid comparison of the murine sequence with its recently cloned rat, human, and chicken counterparts shows a conservation of 17 of 20 asparagine-linked glycosylation consensus sites, eight of eight cysteine residues, and other selected protein domains. The interspecies conserva tion of these domains suggests that they are important for the structure and function of the P2B/LAMP-1 glycoprotein. Northern analysis re vealed that P2B/LAMP-1 is widely expressed in normal murine tissues and tumor cell lines. However, in two experimental models of metastasis, where changes in branching of oligosaccharides on P2B/LAMP-1 have been shown to occur, comparable levels of P2B/LAMP-1 mRNA were found in both metastatic and nonmetastatic cell lines. 4 S. Yagel, R. Feinmesser, C. Waghorne, P. Lalo, M. Breitman, and J. Dennis. Evidence that .(16 branched Asn-linked oligosaccharides facilitate tumor cell invasion of basement membranes by reducing cell adhesion. Int.

American Journal of Physiology Lung Cellular and Molecular Physiology, Feb 1, 2000

The identification of genetic factors important in lung development and function will help in und... more The identification of genetic factors important in lung development and function will help in understanding the underlying molecular mechanisms of respiratory disease. Representational difference analysis of cDNA (cDNA-RDA) is a PCR-based subtractive enrichment procedure for the isolation of differentially expressed genes. We performed cDNA-RDA and isolated genes expressed more abundantly in fetal and adult lungs. Fifty-four clones potentially representing genes with higher transcript levels in the fetal lung were sequenced. Sequence similarity searches indicated that these clones included 12 known genes, a discoidin-like domain-containing gene, six expressed sequence tags (ESTs), and one novel sequence. Fifty-six clones potentially representing genes expressed more abundantly in the adult lung were also cloned and sequenced. Of these, 16 known human genes were represented along with two sequences significantly similar to known mouse genes and two novel sequences. Several of these known genes are implicated in stress response and lung protection. Thus cDNA-RDA was successfully used to isolate known and novel differentially expressed genes, which putatively play an important role in human lung development.

American Journal of Physiology Lung Cellular and Molecular Physiology, Jun 1, 2001

Epithelial cells lining the airways are thought to play a prominent role in respiratory diseases.... more Epithelial cells lining the airways are thought to play a prominent role in respiratory diseases. We utilized cDNA representational difference analysis to identify the genes in which expression is induced by the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta in primary human bronchial epithelial cells and hence are relevant to airway inflammation. Hybridization of the subtraction product to arrayed cDNAs indicated that known tumor necrosis factor-alpha- and interleukin-1beta-inducible genes such as B94, Zfp36, and regulated on activation normal T cell expressed and secreted were represented, confirming the success of the subtraction experiment. A 1,152-clone library potentially representing genes with higher transcript levels in cytokine-treated human bronchial epithelial cells was generated and sequenced. Sequence similarity searches indicated that these clones represented 57 genes of known function, 1 gene of unknown function, 6 expressed sequence tags, and 2 novel sequences. The expression of 19 of these clones was studied by a combination of Northern blotting and RT-PCR analyses and confirmation of differential expression for 10 known genes, 2 expressed sequence tags, and a novel sequence not represented in any of the public databases was obtained. Thus cDNA representational difference analysis was utilized to isolate known and novel differentially expressed genes, which putatively play a role in airway inflammation.

Cell Death Differentiation, 2002

European journal of immunology, Jan 9, 2015

The importance of neutrophil extracellular traps (NETs) in innate immunity is well established bu... more The importance of neutrophil extracellular traps (NETs) in innate immunity is well established but the molecular mechanisms responsible for their formation are still a matter of scientific dispute. Here, we aim to characterize a possible role of the receptor-interacting protein kinase 3 (RIPK3) and the mixed lineage kinase domain-like (MLKL) signaling pathway, which are known to cause necroptosis, in NET formation. Using genetic and pharmacological approaches, we investigated whether this programmed form of necrosis is a prerequisite for NET formation. NETs have been defined as extracellular DNA scaffolds associated with the neutrophil granule protein elastase that are capable of killing bacteria. Neither Ripk3-deficient mouse neutrophils nor human neutrophils in which MLKL had been pharmacologically inactivated, exhibited abnormalities in NET formation upon physiological activation or exposure to low concentrations of PMA. These data indicate that NET formation occurs independently...

D32. HUMAN STUDIES OF IMMUNE DYSFUNCTION IN ASTHMA, 2010

American journal of physiology. Lung cellular and molecular physiology, 2001

Epithelial cells lining the airways are thought to play a prominent role in respiratory diseases.... more Epithelial cells lining the airways are thought to play a prominent role in respiratory diseases. We utilized cDNA representational difference analysis to identify the genes in which expression is induced by the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta in primary human bronchial epithelial cells and hence are relevant to airway inflammation. Hybridization of the subtraction product to arrayed cDNAs indicated that known tumor necrosis factor-alpha- and interleukin-1beta-inducible genes such as B94, Zfp36, and regulated on activation normal T cell expressed and secreted were represented, confirming the success of the subtraction experiment. A 1,152-clone library potentially representing genes with higher transcript levels in cytokine-treated human bronchial epithelial cells was generated and sequenced. Sequence similarity searches indicated that these clones represented 57 genes of known function, 1 gene of unknown function, 6 expressed sequence tags...

Results and problems in cell differentiation, 2009

Cancer cells often exhibit mutations in critical molecules of the apoptotic machinery, resulting ... more Cancer cells often exhibit mutations in critical molecules of the apoptotic machinery, resulting in resistance to common anticancer therapies. In the absence of apoptosis, autophagic cell death can be an alternative form of cell death by excessive self-digestion. Therefore, autophagic cell death can be considered as a backup cell death mechanism when apoptotic cell death mechanisms fail. However, many tumors also exhibit deficiencies in autophagy that may result in both genomic instability and further anticancer drug resistance. This chapter summarizes our current understanding regarding the regulation of autophagy in tumors and discusses potential new anticancer drug treatment strategies.

Cell death & disease, 2014

Dear Editor, DNA-damaging anti-cancer drugs cause cell death by apoptosis, but they also activate... more Dear Editor, DNA-damaging anti-cancer drugs cause cell death by apoptosis, but they also activate macroautophagy 1 (hereafter just autophagy), a fundamental survival pathway under stress where cells enclose cytosol or organelles in double-membrane autophagosomes, then fuse them with lysosomes for recovery of metabolic precursors. 2 This process depends upon autophagy-related (ATG) proteins. 2 Activation of this survival pathway is unwanted in cancer therapy, because even a few surviving tumor cells can accumulate mutations, gain genetic diversity, and, potentially, resume proliferation. We recently reported that expression of ATG5 was upregulated by treatment with low concentrations of etoposide. 4 Few cells entered apoptosis, but almost all showed autophagy. Surprisingly, much of the induced ATG5 was found in the cell nucleus, binding to BIRC5/survivin and causing cell cycle arrest at G 2 /M followed by mitotic catastrophe. 4,5 We then asked whether just ectopic ATG5 expression, without etoposide, would lead to mitotic catastrophe. Indeed, a large part of the expressed ATG5 was again found in the nucleus and rapid cell cycle arrest together with mitotic catastrophe was observed. 4 DNA damage, however, was not in evidence; neither ATM nor ATR phosphorylation was detected and foci of H2AX phosphorylation were absent. 4 This has led us to ask: how can ATG5 induce the same kind of stress response as DNA-damaging drugs?

Allergy, Jan 5, 2015

Eosinophilic esophagitis (EoE) exhibits esophageal dysfunction owing to an eosinophil-predominant... more Eosinophilic esophagitis (EoE) exhibits esophageal dysfunction owing to an eosinophil-predominant inflammation. Activated eosinophils generate eosinophil extracellular traps (EETs) able to kill bacteria. There is evidence of an impaired barrier function in EoE that might allow pathogens to invade the esophagus. This study aimed to investigate the presence and distribution of EETs in esophageal tissues from EoE patients and their association with possible epithelial barrier defects. Anonymized tissue samples from 18 patients with active EoE were analyzed. The presence of DNA nets associated with eosinophil granule proteins forming EETs and the expression of filaggrin, the protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI), antimicrobial peptides, and cytokines were evaluated by confocal microscopy following immune fluorescence staining techniques. EET formation occurred frequently and was detected in all EoE samples correlating with the numbers of infiltrating ...

Journal of immunology (Baltimore, Md. : 1950), 2011

The most common form of neutrophil death, under both physiological and inflammatory conditions, i... more The most common form of neutrophil death, under both physiological and inflammatory conditions, is apoptosis. In this study, we report a novel form of programmed necrotic cell death, associated with cytoplasmic organelle fusion events, that occurs in neutrophils exposed to GM-CSF and other inflammatory cytokines upon ligation of CD44. Strikingly, this type of neutrophil death requires PI3K activation, a signaling event usually involved in cellular survival pathways. In the death pathway reported in this study, PI3K is required for the generation of reactive oxygen species, which somehow trigger the generation of large cytoplasmic vacuoles, generated by the fusion of CD44-containing endosomes with autophagosomes and secondary, but not primary, granules. Neutrophils demonstrating vacuolization undergo rapid cell death that depends on receptor-interacting protein 1 kinase activity and papain family protease(s), but not caspases, that are most likely activated and released, respectively...

Encyclopedia of Medical Immunology, 2014

Encyclopedia of Medical Immunology, 2014

Encyclopedia of Medical Immunology, 2014

Cancer Research

Swainsonine, an inhibitor of a-mannosidases, has been shown to block experimental metastasis of H... more Swainsonine, an inhibitor of a-mannosidases, has been shown to block experimental metastasis of H161 10 melanoma and MDAY-D2 lymphoid tumor cells in syngeneic mice. In this report we demonstrate that swainsonine also reduces the growth rate of human melanoma cells in vitro and in vivo. Graded doses of Swainsonine were administered either orally or via implanted Alzet miniosmotic pumps to athymic nude mice bearing subcutaneously implanted human MeWo melanoma cells. Swainsonine at 10 «ig/ml in the drinking water or 0.5 mg/kg/day administered by miniosmotic pump reduced the growth rate of the Me\Yo tumors by approximately 50% and inhibited the expression of complex-type oligosaccharides in tumors and host intestine by only 10-20%. Swainsonine doses of 4 mg/kg/day reduced expression of complex-type oligosaccharides by 85% in vivo but afforded no additional inhibitory effect. A glycosylation mutant of MeWo called 3S5 has a defect in the synthesis of complex-type asparagine-linked oligosaccharides resulting in incom plete processing similar to that observed in swainsonine-treated MeWo tumor cells. Swainsonine did not inhibit the proliferation of 3S5 cells in vitro nor the growth of 3S5 tumors in nude mice. The results suggest that expression of highly branched complex-type oligosaccharides com monly associated with the malignant phenotype may provide the tumor cells with a growth advantage.

Cancer Research

Sialylated and G\cNAcßl-6Manal-6Manßl (pil-k branched) com plex-type oligosaccharides linked to... more Sialylated and G\cNAcßl-6Manal-6Manßl (pil-k branched) com plex-type oligosaccharides linked to asparagine residues of membrane glycoproteins in metastatic murine tumor cells have been associated with efficient tumor cell metastasis. A large proportion of these oligosaccharide structures, in several unrelated malignant cell lines, have been shown to be associated with a glycoprotein termed P2B, with a molecular weight of 130,000. This glycoprotein has recently been purified from the met astatic MDAY-D2 cell line and shown to be biochemically similar to a lysosomal associated membrane glycoprotein (LAMP-1). We report here the details of a 2147 nucleotide complementary DNA encoding the entire murine P2B polypeptide which was immunoselected from a Xgtl 1 expres sion library and sequenced. The sequence is similar to a complementary DNA coding for mouse LAMP-1 with the exception of a 5' untranslated region, a leader signal-sequence, and various insertions, deletions, and substitutions in the 3' untranslated domain. An open reading frame of 405 amino acids encodes a mature polypeptide of 382 residues with a predicted molecular weight of 42,000. P2B/LAMP-1 possesses 20 asparagine-linked glycosylation sites separated into equal halves by a central, putative hinge region and is anchored by a carboxy, membranespanning, domain. Topologica! considerations dictate that cell surface expression of P2B/LAMP-1 exposes the bulk of the glycoprotein into the extracellular compartment. Immunofluorescent staining of fibroblast cells indicated that P2B/LAMP-1 was associated with lysosomal mem branes and, to a lesser degree, select surfaces of plasma membrane. An amino acid comparison of the murine sequence with its recently cloned rat, human, and chicken counterparts shows a conservation of 17 of 20 asparagine-linked glycosylation consensus sites, eight of eight cysteine residues, and other selected protein domains. The interspecies conserva tion of these domains suggests that they are important for the structure and function of the P2B/LAMP-1 glycoprotein. Northern analysis re vealed that P2B/LAMP-1 is widely expressed in normal murine tissues and tumor cell lines. However, in two experimental models of metastasis, where changes in branching of oligosaccharides on P2B/LAMP-1 have been shown to occur, comparable levels of P2B/LAMP-1 mRNA were found in both metastatic and nonmetastatic cell lines. 4 S. Yagel, R. Feinmesser, C. Waghorne, P. Lalo, M. Breitman, and J. Dennis. Evidence that .(16 branched Asn-linked oligosaccharides facilitate tumor cell invasion of basement membranes by reducing cell adhesion. Int.

American Journal of Physiology Lung Cellular and Molecular Physiology, Feb 1, 2000

The identification of genetic factors important in lung development and function will help in und... more The identification of genetic factors important in lung development and function will help in understanding the underlying molecular mechanisms of respiratory disease. Representational difference analysis of cDNA (cDNA-RDA) is a PCR-based subtractive enrichment procedure for the isolation of differentially expressed genes. We performed cDNA-RDA and isolated genes expressed more abundantly in fetal and adult lungs. Fifty-four clones potentially representing genes with higher transcript levels in the fetal lung were sequenced. Sequence similarity searches indicated that these clones included 12 known genes, a discoidin-like domain-containing gene, six expressed sequence tags (ESTs), and one novel sequence. Fifty-six clones potentially representing genes expressed more abundantly in the adult lung were also cloned and sequenced. Of these, 16 known human genes were represented along with two sequences significantly similar to known mouse genes and two novel sequences. Several of these known genes are implicated in stress response and lung protection. Thus cDNA-RDA was successfully used to isolate known and novel differentially expressed genes, which putatively play an important role in human lung development.

American Journal of Physiology Lung Cellular and Molecular Physiology, Jun 1, 2001

Epithelial cells lining the airways are thought to play a prominent role in respiratory diseases.... more Epithelial cells lining the airways are thought to play a prominent role in respiratory diseases. We utilized cDNA representational difference analysis to identify the genes in which expression is induced by the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta in primary human bronchial epithelial cells and hence are relevant to airway inflammation. Hybridization of the subtraction product to arrayed cDNAs indicated that known tumor necrosis factor-alpha- and interleukin-1beta-inducible genes such as B94, Zfp36, and regulated on activation normal T cell expressed and secreted were represented, confirming the success of the subtraction experiment. A 1,152-clone library potentially representing genes with higher transcript levels in cytokine-treated human bronchial epithelial cells was generated and sequenced. Sequence similarity searches indicated that these clones represented 57 genes of known function, 1 gene of unknown function, 6 expressed sequence tags, and 2 novel sequences. The expression of 19 of these clones was studied by a combination of Northern blotting and RT-PCR analyses and confirmation of differential expression for 10 known genes, 2 expressed sequence tags, and a novel sequence not represented in any of the public databases was obtained. Thus cDNA representational difference analysis was utilized to isolate known and novel differentially expressed genes, which putatively play a role in airway inflammation.

Cell Death Differentiation, 2002

European journal of immunology, Jan 9, 2015

The importance of neutrophil extracellular traps (NETs) in innate immunity is well established bu... more The importance of neutrophil extracellular traps (NETs) in innate immunity is well established but the molecular mechanisms responsible for their formation are still a matter of scientific dispute. Here, we aim to characterize a possible role of the receptor-interacting protein kinase 3 (RIPK3) and the mixed lineage kinase domain-like (MLKL) signaling pathway, which are known to cause necroptosis, in NET formation. Using genetic and pharmacological approaches, we investigated whether this programmed form of necrosis is a prerequisite for NET formation. NETs have been defined as extracellular DNA scaffolds associated with the neutrophil granule protein elastase that are capable of killing bacteria. Neither Ripk3-deficient mouse neutrophils nor human neutrophils in which MLKL had been pharmacologically inactivated, exhibited abnormalities in NET formation upon physiological activation or exposure to low concentrations of PMA. These data indicate that NET formation occurs independently...

D32. HUMAN STUDIES OF IMMUNE DYSFUNCTION IN ASTHMA, 2010

American journal of physiology. Lung cellular and molecular physiology, 2001

Epithelial cells lining the airways are thought to play a prominent role in respiratory diseases.... more Epithelial cells lining the airways are thought to play a prominent role in respiratory diseases. We utilized cDNA representational difference analysis to identify the genes in which expression is induced by the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta in primary human bronchial epithelial cells and hence are relevant to airway inflammation. Hybridization of the subtraction product to arrayed cDNAs indicated that known tumor necrosis factor-alpha- and interleukin-1beta-inducible genes such as B94, Zfp36, and regulated on activation normal T cell expressed and secreted were represented, confirming the success of the subtraction experiment. A 1,152-clone library potentially representing genes with higher transcript levels in cytokine-treated human bronchial epithelial cells was generated and sequenced. Sequence similarity searches indicated that these clones represented 57 genes of known function, 1 gene of unknown function, 6 expressed sequence tags...

Results and problems in cell differentiation, 2009

Cancer cells often exhibit mutations in critical molecules of the apoptotic machinery, resulting ... more Cancer cells often exhibit mutations in critical molecules of the apoptotic machinery, resulting in resistance to common anticancer therapies. In the absence of apoptosis, autophagic cell death can be an alternative form of cell death by excessive self-digestion. Therefore, autophagic cell death can be considered as a backup cell death mechanism when apoptotic cell death mechanisms fail. However, many tumors also exhibit deficiencies in autophagy that may result in both genomic instability and further anticancer drug resistance. This chapter summarizes our current understanding regarding the regulation of autophagy in tumors and discusses potential new anticancer drug treatment strategies.

Cell death & disease, 2014

Dear Editor, DNA-damaging anti-cancer drugs cause cell death by apoptosis, but they also activate... more Dear Editor, DNA-damaging anti-cancer drugs cause cell death by apoptosis, but they also activate macroautophagy 1 (hereafter just autophagy), a fundamental survival pathway under stress where cells enclose cytosol or organelles in double-membrane autophagosomes, then fuse them with lysosomes for recovery of metabolic precursors. 2 This process depends upon autophagy-related (ATG) proteins. 2 Activation of this survival pathway is unwanted in cancer therapy, because even a few surviving tumor cells can accumulate mutations, gain genetic diversity, and, potentially, resume proliferation. We recently reported that expression of ATG5 was upregulated by treatment with low concentrations of etoposide. 4 Few cells entered apoptosis, but almost all showed autophagy. Surprisingly, much of the induced ATG5 was found in the cell nucleus, binding to BIRC5/survivin and causing cell cycle arrest at G 2 /M followed by mitotic catastrophe. 4,5 We then asked whether just ectopic ATG5 expression, without etoposide, would lead to mitotic catastrophe. Indeed, a large part of the expressed ATG5 was again found in the nucleus and rapid cell cycle arrest together with mitotic catastrophe was observed. 4 DNA damage, however, was not in evidence; neither ATM nor ATR phosphorylation was detected and foci of H2AX phosphorylation were absent. 4 This has led us to ask: how can ATG5 induce the same kind of stress response as DNA-damaging drugs?

Allergy, Jan 5, 2015

Eosinophilic esophagitis (EoE) exhibits esophageal dysfunction owing to an eosinophil-predominant... more Eosinophilic esophagitis (EoE) exhibits esophageal dysfunction owing to an eosinophil-predominant inflammation. Activated eosinophils generate eosinophil extracellular traps (EETs) able to kill bacteria. There is evidence of an impaired barrier function in EoE that might allow pathogens to invade the esophagus. This study aimed to investigate the presence and distribution of EETs in esophageal tissues from EoE patients and their association with possible epithelial barrier defects. Anonymized tissue samples from 18 patients with active EoE were analyzed. The presence of DNA nets associated with eosinophil granule proteins forming EETs and the expression of filaggrin, the protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI), antimicrobial peptides, and cytokines were evaluated by confocal microscopy following immune fluorescence staining techniques. EET formation occurred frequently and was detected in all EoE samples correlating with the numbers of infiltrating ...

Journal of immunology (Baltimore, Md. : 1950), 2011

The most common form of neutrophil death, under both physiological and inflammatory conditions, i... more The most common form of neutrophil death, under both physiological and inflammatory conditions, is apoptosis. In this study, we report a novel form of programmed necrotic cell death, associated with cytoplasmic organelle fusion events, that occurs in neutrophils exposed to GM-CSF and other inflammatory cytokines upon ligation of CD44. Strikingly, this type of neutrophil death requires PI3K activation, a signaling event usually involved in cellular survival pathways. In the death pathway reported in this study, PI3K is required for the generation of reactive oxygen species, which somehow trigger the generation of large cytoplasmic vacuoles, generated by the fusion of CD44-containing endosomes with autophagosomes and secondary, but not primary, granules. Neutrophils demonstrating vacuolization undergo rapid cell death that depends on receptor-interacting protein 1 kinase activity and papain family protease(s), but not caspases, that are most likely activated and released, respectively...

Encyclopedia of Medical Immunology, 2014

Encyclopedia of Medical Immunology, 2014

Encyclopedia of Medical Immunology, 2014